Hereditary alpha-tryptasemia: a commonly inherited modifier of anaphylaxis
Abstract
Purpose of review Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase in Western populations. It is a risk factor for severe anaphylaxis among individuals with venom allergy and an established modifier of anaphylaxis and mast cell mediator-associated symptoms among patients with systemic mastocytosis. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HαT is the first step in identifying optimal medical management and targets for novel therapeutics.Recent findings HαT prevalence is increased in both clonal and non-clonal mast cell-associated disorders where it augments symptoms of immediate hypersensitivity, including anaphylaxis. The unique properties of naturally occurring α/β-tryptase heterotetramers may explain certain elements of phenotypes associated with HαT, though additional mechanisms are being evaluated. This review provides an overview of the clinical and translational studies that have identified HαT as a modifier of mast cell-associated disorders and anaphylaxis and discusses mechanisms that may potentially explain some of these clinical findings.
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The number of TPSAB1 copies determines an increase in α-tryptase levels, leading to elevated BST, with each additional copy adding approximately 9-10 ng/ml to basal BST levels.
“Further studies have elucidated as the number of TPSAB1 copies determined an increase in α-tryptase levels, on turn ultimately leading to elevated BST, each additional copy number adding approximately 9–10 ng/ml to the basal BST levels (12, 13).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [12]
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Matheny, M. V., Henao, M. P., & Al‐Shaikhly, T. (2025) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-025-09063-0 · Cited by 2 · see citing works
Rydz, A., & Lange, M. (2023) · Forum Dermatologicum · doi:10.5603/fd.96810 · Cited by 1 · see citing works
Predictors of Clonality and Underlying Mastocytosis in Mast Cell Activation Syndromes
González‐de‐Olano, D., & Álvarez‐Twöse, I. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-023-01122-w · Cited by 1 · see citing works
Prevalence of Autoantibodies in Patients with Hereditary Alpha-Tryptasemia
Slapnicar, C. A., Lee, E. Y., & Vadas, P. (2024) · International Archives of Allergy and Immunology · doi:10.1159/000541880 · Cited by 1 · see citing works
Hereditary alpha-tryptasemia and monoclonal mast cell disorders
Chantran, Y., & Arock, M. (2025) · Frontiers in Allergy · doi:10.3389/falgy.2025.1600680 · Cited by 1 · see citing works
Fatal, persistent, refractory, and biphasic anaphylaxis
Dribin, T. E. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-96018-2.00002-x
Newer entities in dermatology: A short review on the newly defined dermatoses and acronyms
Singh, S., Gupta, M., Bishnoi, A., & Handa, S. (2025) · Indian Journal of Dermatology Venereology and Leprology · doi:10.25259/ijdvl_710_2024
Hereditary Alpha Tryptasemia: Survey of Concomitant Genetic Testing
Butterfield, J. H., Bhasin, A. K., Ishmael, L., & Squire, J. D. (2025) · International Archives of Allergy and Immunology · doi:10.1159/000544704
Hymenoptera Venom Anaphylaxis: What Makes Them Different
Vicens-Novell, G., Fuentes, A. P., Delgado, P. S., & Ruiz-León, B. (2025) · Current Treatment Options in Allergy · doi:10.1007/s40521-025-00385-0
Hereditary alpha tryptasemia and clinical implications
Önata, E. T., Özdemır, Ö., & Savaşan, S. (2025) · World Journal of Clinical Cases · doi:10.12998/wjcc.v13.i21.104723
Alfa triptazemijos aktualumas klinikinėje praktikoje
Šematonytė, J., Vaidotaitė, G., Vainoriūtė, G., & Traberg, R. (2025) · Pulmonology and allergology · doi:10.37499/pia.1699
Hereditary Alpha Tryptasemia in a Child With Idiopathic Anaphylaxis
Hitchcock, D. R., & Hauk, P. J. (2025) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2025.08.012
Genetic, morphological and functional characteristics of human tryptase
Евгеньевна, Т. Н., Lebedenko, A. A., Евгеньевна, С. О., DOBAEVA, N. M., Skosar, V. O., Haygetyan, N. Y., Krivokhlyabov, I., & Shkilnyuk, S. P. (2025) · Allergology and Immunology in Pediatrics · doi:10.53529/2500-1175-2025-2-4-14
Intra familial expression of Alpha tryptasemiaPreprint
NDI, P. K., AMOUGOU, C. M., Mounir, M., Michel, O., & Cogan, E. (2026) · Research Square · doi:10.21203/rs.3.rs-8193743/v1
Platzgummer, S., SIPMeL, A. N. D. G.-A., Onida, R., Bruno, L., Caponi, L., Anzivino, P., Conte, M., ZANONI, G., Ghisellini, S., Deleonardi, G., et al. (2026) · La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine · doi:10.23736/s1825-859x.25.00312-3
Hereditary Alpha-Tryptasemia and Mastocytosis: What We Know and What We Need To Learn
Rama, T. A., & Gülen, T. (2026) · Current Allergy and Asthma Reports · doi:10.1007/s11882-026-01262-9 · Cited by 1 · see citing works
Simeone, I. M., Galeas‐Pena, M., White, K., Sullivan, B., Morelli, A., Silvester, J. A., Konnikova, L., Therrien, A., & Glover, S. C. (2026) · Frontiers in Allergy · doi:10.3389/falgy.2026.1783914
- Authors
- Wu, R., & Lyons, J. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lyons, Jonathan J.
- Venue
- Current Allergy and Asthma Reports
- Published
- 2021-05
- Volume
- 21
- Issue
- 5
- Pages
- 33-33
- ISSN
- 1529-7322 (ISSN-L)
- 1534-6315
- OpenAlex
- W3162279999
- Cited by
- 43
- References
- 58
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 5 · 2023: 6 · 2022: 11 · 2021: 2
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Allergy and Asthma Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- hereditary alpha-tryptasemia, anaphylaxis, serum tryptase, venom allergy, systemic mastocytosis, immediate hypersensitivity, genetic modifiers
- MeSH terms
- Anaphylaxis, Genotype, Humans, Mast Cells, Mastocytosis, Phenotype, Tryptases
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